tbuckley/cabot-search huggingface dataset:
Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial
Authors: Catherine M Broome, Vickie McDonald, Yoshitaka Miyakawa, Monica Carpenedo, David J Kuter, Hanny Al-Samkari, James B Bussel, Marie Godar, Jaume Ayguasanosa, Kristof De Beuf, Francesco Rodeghiero, Marc Michel, Adrian Newland, Michael Fillitz, Paul Knoebl, Stef Meers, Ismail Mohamad Amine, Jaromir Gumulec, Antonin Hlusi, Jiri Mayer, Philippe Quittet, Jean-Francois Viallard, Magdana Betaneli, Irine Datikashvili-David, Genadi Iosava, Levan Makhaldiani, Laszlo Rejto, Nino Sharashenidze, Stefanie Groepper, Alexander Röth, Aryan Hamed, Arpad Illes, Monica Carpenedo, Andrea Artoni, Monica Bocchia, Barbara Gamberi, Alessandra Borchiellini, Esther Natalie Oliva, Andrea Patriarca, Simona Tomassetti, Yoshitaka Miyakawa, Kiyoshi Ando, Hiroshi Handa, Shinya Katsutani, Kaichi Nishiwaki, Shoko Ito, Tomoki Ito, Fransien de Boer, A.J. Gerard Jansen, Hanna Ciepluch, Szymon Fornagiel, Sebastian Grosicki, Maria Soroka-Wojtaszko, Jacek Trelinski, Bulat Bakirov, Elena Borisenkova, Elena Volodicheva, Yuri Shatokhin, Andrey Proydakov, Maria Aranzazu Alonso, María Eva Mingot-Castellano, Blanca Sanchez-Gonzalez, David Valcarcel Ferreiras, Meltem Ayli, Tuba Hacibekiroglu, Ahmet Muzaffer Demir, Meliha Nalçaci, Mehmet Sonmez, Anil Tombak, Selami Kocak Toprak, Burhan Turgut, Filiz Vural, Munci Yagci, Fevzi Altuntas, Mehmet Turgut, Emin Kaya, Nataliya Romanyuk, Vickie McDonald, Syed Rashid Saeed Kazmi, Catherine Broome, Spero Cataland, Ketan Doshi, Steven R. Lentz, Michael Boxer, Richard Rosenberg
Journal: The Lancet (2023)
Mpox as AIDS-defining event with a severe and protracted course: clinical, immunological, and virological implications
Authors: Carmela Pinnetti, Eleonora Cimini, Valentina Mazzotta, Giulia Matusali, Alessandra Vergori, Annalisa Mondi, Martina Rueca, Sandro Batzella, Eleonora Tartaglia, Aurora Bettini, Stefania Notari, Marika Rubino, Massimo Tempestilli, Carlo Pareo, Laura Falasca, Franca Del Nonno, Alessandra Scarabello, Marta Camici, Roberta Gagliardini, Enrico Girardi, Francesco Vaia, Fabrizio Maggi, Chiara Agrati, Andrea Antinori
Journal: The Lancet Infectious Diseases (2023)
Hyaluronan decorated layer-by-layer assembled lipid nanoparticles for miR-181a delivery in glioblastoma treatment
Authors: Victor Passos Gibson, Houda Tahiri, Chun Yang, Quoc Thang Phan, Xavier Banquy, Pierre Hardy
Journal: Biomaterials (2023)

Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer. Current pharmacological interventions marginally increase the 12-month overall survival of patients with GBM. Among the novel therapeutic strategies being pursued, micro-RNAs, a class of non-coding RNAs, are receiving considerable attention for their regulation of several pathways implicated in tumorigenesis and survival. Notably, microRNA-181a-5p (miR-181a) has consistently been reported to be downregulated in GBM clinical samples, and its overexpression negatively affects tumor growth both in vitro and in vivo. To improve the delivery of miR-181a to GBM cells, we sought to develop a modified lipid-based nanocarrier capable of encapsulating and delivering miR-181a to GBM cells in vitro and in vivo. Optimized ionizable-lipid containing lipid nanoparticles (LNP) were constructed by covering the miR-181a-loaded LNP with alternating layers of miR-181a, poly-l-arginine and hyaluronic acid through the layer-by-layer technique. The resulting hyaluronan-decorated lipid nanoparticles (HA-LNP) targeted GBM cells more efficiently than non-modified LNP and mediated siRNA and miRNA transfection in vitro. Finally, delivery of miR-181a by HA-LNP induced significant cellular death of U87 GBM cells in vitro and delayed tumor growth in an in vivo subcutaneous tumor model.
Table of Contents
Authors: A González-Martín, P Harter, A Leary, D Lorusso, R Miller, B Pothuri, I Ray-Coquard, D Tan, E Bellet, A Oaknin, J Ledermann, S Loibl, H Azim, T Bachelot, P Berveiller, A Bosch, E Cardonick, C Denkert, M Halaska, M Hoeltzenbein, A Johansson, C Maggen, U Markert, F Peccatori, P Poortmans, E Saloustros, C Saura, P Schmid, E Stamatakis, M Van Den Heuvel-Eibrink, M Van Gerwen, V Vandecaveye, G Pentheroudakis, G Curigliano, F Amant, M Strobl, J Gallaher, M Robertson-Tessi, J West, A Anderson, K Jhaveri, L Eli, H Wildiers, S Hurvitz, A Guerrero-Zotano, N Unni, A Brufsky, H Park, J Waisman, E Yang, I Spanggaard, S Reid, M Burkard, S Vinayak, A Prat, M Arnedos, F.-C Bidard, S Loi, J Crown, M Bhave, S Piha-Paul, J Suga, S Chia, J Garcia-Saenz, V Gambardella, M De Miguel, E Gal-Yam, A Raphael, S Stemmer, C Ma, A Hanker, D Ye, J Goldman, R Bose, L Peterson, J Bell, A Frazier, D Diprimeo, A Wong, C Arteaga, D Solit, H Parsons, T Blewett, X Chu, S Sridhar, K Santos, K Xiong, V Abramson, A Patel, J Cheng, J Rhoades, J Force, R Liu, T Traina, L Carey, M Rimawi, K Miller, V Stearns, J Specht, C Falkson, H Burstein, A Wolff, E Winer, N Tayob, I Krop, G Makrigiorgos, T Golub, E Mayer, V Adalsteinsson, E Felip, N Altorki, C Zhou, E Vallières, A Martínez-Martí, A Rittmeyer, A Chella, M Reck, O Goloborodko, M Huang, R Belleli, V Mcnally, M Srivastava, E Bennett, B Gitlitz, H Wakelee
Journal: Annals of Oncology (2023)
All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration
Authors: Sophia M Rein, Fiona C Lampe, Suzanne M Ingle, Jonathan A C Sterne, Adam Trickey, M John Gill, Vasileios Papastamopoulos, Linda Wittkop, Marc van der Valk, Maria Kitchen, Jodie L Guest, Derek D Satre, Gilles Wandeler, Pepa Galindo, Jessica Castilho, Heidi M Crane, Colette J Smith
Journal: The Lancet Public Health (2023)

Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.
67th Society for Social Medicine &amp; Population Health Annual Scientific meeting
Authors: Christina Kassiteridi
Journal: The Lancet Public Health (2023)

Clair Woods-Brown (Institute for Social Marketing, University of Stirling, Stirling, UK) and colleagues presented the results of their review on smoking or vaping and related factors after release from smoke-free prisons. They included studies that assessed if people smoked or vaped or planned to smoke or vape after release. The authors identified nine studies (mainly from the USA or Australia), from which seven reported on pre-release intentions to remain smoke-free, and all studies reported the prevalence of smoking after release.
Brief bouts of device-measured intermittent lifestyle physical activity and its association with major adverse cardiovascular events and mortality in people who do not exercise: a prospective cohort study
Authors: Matthew N Ahmadi, Mark Hamer, Jason M R Gill, Marie Murphy, James P Sanders, Aiden Doherty, Emmanuel Stamatakis
Journal: The Lancet Public Health (2023)

BackgroundGuidelines emphasise the health benefits of bouts of physical activity of any duration. However, the associations of intermittent lifestyle physical activity accumulated through non-exercise with mortality and major adverse cardiovascular events (MACE) remain unclear. We aimed to examine the associations of bouts of moderate-to-vigorous intermittent lifestyle physical activity (MV-ILPA) and the proportion of vigorous activity contributing within these bouts with mortality and MACE.MethodsIn this prospective cohort study, we used data from the UK Biobank on adults who do not exercise (ie, those who did not report leisure-time exercise) who had wrist-worn accelerometry data available. Participants were followed up until Nov 30, 2022, with the outcome of interest of all-cause mortality obtained through linkage with NHS Digital of England and Wales, and the NHS Central Register and National Records of Scotland, and MACE obtained from inpatient hospitalisation data provided by the Hospital Episode Statistics for England, the Patient Episode Database for Wales, and the Scottish Morbidity Record for Scotland. MV-ILPA bouts were derived using a two-level Random Forest classifier and grouped as short (<1 min), medium (1 to <3 min; 3 to <5 min), and long (5 to <10 min). We further examined the dose–response relationship of the proportion of vigorous physical activity contributing to the MV-ILPA bout.FindingsBetween June 1, 2013, and Dec 23, 2015, 103 684 Biobank participants wore an accelerometer on their wrist. 25 241 adults (mean age 61·8 years [SD 7·6]), of whom 14 178 (56·2%) were women, were included in our analysis of all-cause mortality. During a mean follow-up duration of 7·9 years (SD 0·9), 824 MACE and 1111 deaths occurred. Compared with bouts of less than 1 min, mortality risk was lower for bouts of 1 min to less than 3 min (hazard ratio [HR] 0·66 [0·53–0·81]), 3 min to less than 5 min (HR 0·56 [0·46–0·69]), and 5 to less than 10 min (HR 0·48 [0·39–0·59]). Similarly, compared with bouts of less than 1 min, risk of MACE was lower for bouts of 1 min to less than 3 min (HR 0·71 [0·54–0·93]), 3 min to less than 5 min (0·62 [0·48–0·81]), and 5 min to less than 10 min (0·59 [0·46–0·76]). Short bouts (<1 min) were associated with lower MACE risk only when bouts were comprised of at least 15% vigorous activity.InterpretationIntermittent non-exercise physical activity was associated with lower mortality and MACE. Our results support the promotion of short intermittent bouts of non-exercise physical activity of moderate-to-vigorous intensity to improve longevity and cardiovascular health among adults who do not habitually exercise in their leisure time.FundingAustralian National Health, Medical Research Council, and Wellcome Trust.
National public health response to an outbreak of toxigenic Corynebacterium diphtheriae among asylum seekers in England, 2022: a descriptive epidemiological study
Authors: Shennae O'Boyle, Hannah E Barton, Joshua C D'Aeth, Rebecca Cordery, Norman K Fry, David Litt, Rosamund Southgate, Robert Verrecchia, Trish Mannes, Tian Yun Wang, Daniel E Stewart, Oluwakemi Olufon, Michelle Dickinson, Mary E Ramsay, Gayatri Amirthalingam
Journal: The Lancet Public Health (2023)

In July, 2022, an increase in diphtheria cases caused by toxigenic Corynebacterium diphtheriae (C diphtheriae) was reported among asylum seekers arriving by small boats to England. Rising case numbers presented challenges for case and contact management in initial reception centres, prompting changes to national guidance and implementation of population-based control measures. This study aimed to describe the outbreak of toxigenic C diphtheriae among asylum seekers arriving by small boats to England during 2022 by use of national surveillance data.We undertook a descriptive epidemiological analysis of cases of toxigenic C diphtheriae among asylum seekers arriving by small boats to England during 2022, incorporating genomic sequencing data, antibiotic susceptibility testing results, and epidemiological data obtained through the UK Health Security Agency's national enhanced surveillance programme. Health Protection Teams conducted risk assessments, and operational data (including details regarding offer and uptake of antibiotics and vaccinations) were obtained from National Health Service partners supporting the intervention programme.In 2022, C diphtheriae isolates from 86 asylum seekers arriving by small boats were submitted to the National Reference Laboratory for confirmation and testing. Toxigenic C diphtheriae was confirmed for 72 (84%) cases and one individual with typical diphtheritic lesions but from whom no C diphtheriae was isolated from clinical swabs was also included as a probable case, resulting in 73 cases of diphtheria. 71 (97%) were male, 39 (53%) were younger than 18 years, and 36 (49%) presented with cutaneous diphtheria. The prevalence of diphtheria was highest among Afghans (1·3%) compared with all other nationalities (<0·1%). Local antibiotic susceptibility testing identified six cases with a macrolide resistant strain.The increase in diphtheria coincided with a high volume of asylum seekers arriving by small boats to England during 2022, and subsequently increased clinical awareness of the disease among this population. Long-term disruption to vaccination programmes in origin countries along with barriers to accessing health care along migrant routes puts asylum seekers arriving by small boats at risk of disease. With arrivals expected to continue in 2023, the UK Health Security Agency has recommended continuation of population-based control measures in England until October, 2023, subject to ongoing review.The UK Health Security Agency.
Homelessness in Europe: time to act
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2023)

On Sept 5, 2023, the Federation of National Organisations Working with the Homeless released their latest overview of housing exclusion in Europe estimating that 895 000 people—about one in every 600 people, are living rough, in shelters, or temporary accommodation in Europe every night. The staggering number highlights this ongoing public health issue but is likely just showing a fraction of the full problem. Data are missing out on capturing the full range of experiences and gendered homelessness.
The need to promote sleep health in public health agendas across the globe
Authors: Diane C Lim, Arezu Najafi, Lamia Afifi, Claudio LA Bassetti, Daniel J Buysse, Fang Han, Birgit Högl, Yohannes Adama Melaku, Charles M Morin, Allan I Pack, Dalva Poyares, Virend K Somers, Peter R Eastwood, Phyllis C Zee, Chandra L Jackson
Journal: The Lancet Public Health (2023)

Healthy sleep is essential for physical and mental health, and social wellbeing; however, across the globe, and particularly in developing countries, national public health agendas rarely consider sleep health. Sleep should be promoted as an essential pillar of health, equivalent to nutrition and physical activity. To improve sleep health across the globe, a focus on education and awareness, research, and targeted public health policies are needed. We recommend developing sleep health educational programmes and awareness campaigns; increasing, standardising, and centralising data on sleep quantity and quality in every country across the globe; and developing and implementing sleep health policies across sectors of society. Efforts are needed to ensure equity and inclusivity for all people, particularly those who are most socially and economically vulnerable, and historically excluded.
Potential population-level effectiveness of one-dose HPV vaccination in low-income and middle-income countries: a mathematical modelling analysis
Authors: Élodie Bénard, Mélanie Drolet, Jean-François Laprise, Guillaume Gingras, Mark Jit, Marie-Claude Boily, Paul Bloem, Marc Brisson
Journal: The Lancet Public Health (2023)

Given the accumulating evidence that one-dose vaccination could provide high and sustained protection against human papillomavirus (HPV) infection and related diseases, we examined the population-level effectiveness and efficiency of one-dose HPV vaccination of girls compared with two-dose vaccination, using mathematical modelling.
The association between higher education attendance and common mental health problems among young people in England: evidence from two population-based cohorts
Authors: Tayla McCloud, Strahil Kamenov, Claire Callender, Glyn Lewis, Gemma Lewis
Journal: The Lancet Public Health (2023)

BackgroundIt is unclear whether young people who attend higher education are at increased risk of common mental disorders, compared with those who do not attend. We aimed to investigate whether higher education attendance was associated with increased symptoms of common mental disorders (depression and anxiety) in young people before, during and after attendance.MethodsFor this cohort study, we used two cohorts—the Longitudinal Studies of Young People in England (LSYPE1: N=4832, 55·8% [2696 of 4832] students; LSYPE2: n=6128, 50·7% [3104 of 6128] students), beginning in 2004 for LSYPE1 and 2013 for LSYPE2. Both cohorts were designed to be nationally representative, with schools in England as the primary sampling unit. Symptoms of common mental disorders were assessed with the General Health Questionnaire (GHQ-12) before (age 14–17 years for both cohorts), during (age 18–19 years for LSYPE2), and after (age 25 years for LSYPE1) higher education. We assessed differences in GHQ scores using unadjusted and confounder adjusted linear regression.FindingsAt ages 18–19 years (LSYPE2), mean GHQ-12 scores were 12·0 (SD 6·4) among students and 11·6 (SD 6·8) among non-students (adjusted mean difference 0·36, 95% CI 0·05 to 0·68; p=0·024). In LSYPE1, young people who attended higher education at ages 18–20 years had higher symptoms of common mental disorders at ages 16–17 years than those who did not (0·60, 0·30 to 0·90). However, after higher education (age 25 years for LSYPE1), there was no evidence of a difference—mean GHQ-12 scores were 11·4 (SD 5·5) among those who had attended and 11·7 (SD 6·4) among those who had not attended (–0·25, –0·66 to 0·16; p=0·23).InterpretationWe found evidence that students had more symptoms of common mental disorders than non-students at ages 18–19 years, albeit the effect size was small and there was no evidence of a longer-term difference at the age of 25 years.FundingDepartment for Education.
A Chromosome-Level Genome Assembly of the Reef Stonefish (<i>Synanceia verrucosa</i>) Provides Novel Insights into Stonustoxin (<i>sntx</i>) Genes
Authors: Tianle Tang, Yu Huang, Chao Peng, Yanling Liao, Yunyun Lv, Qiong Shi, Bingmiao Gao
Journal: Molecular Biology and Evolution (2023)

Abstract Reef stonefish (Synanceia verrucosa) is one of the most venomous fishes, but its biomedical study has been restricted to molecular cloning and purification of its toxins, instead of high-throughput genetic research on related toxin genes. In this study, we constructed a chromosome-level haplotypic genome assembly for the reef stonefish. The genome was assembled into 24 pseudo-chromosomes, and the length totaled 689.74 Mb, reaching a contig N50 of 11.97 Mb and containing 97.8% of complete BUSCOs. A total of 24,050 protein-coding genes were annotated, of which metalloproteinases, C-type lectins, and stonustoxins (sntx) were the most abundant putative toxin genes. Multitissue transcriptomic and venom proteomic data showed that sntx genes, especially those clustered within a 50-kb region on the chromosome 2, had higher transcription levels than other types of toxins as well as those sntx genes scatteringly distributed on other chromosomes. Further comparative genomic analysis predicted an expansion of sntx-like genes in the Percomorpha lineage including nonvenomous fishes, but Scorpaenoidei species experienced extra independent sntx duplication events, marking the clear-cut origin of authentic toxic stonustoxins. In summary, this high-quality genome assembly and related comparative analysis of toxin genes highlight valuable genetic differences for potential involvement in the evolution of venoms among Scorpaeniformes fishes.
Evolution of the Mutation Spectrum Across a Mammalian Phylogeny
Authors: Annabel C Beichman, Jacqueline Robinson, Meixi Lin, Andrés Moreno-Estrada, Sergio Nigenda-Morales, Kelley Harris
Journal: Molecular Biology and Evolution (2023)

Abstract Although evolutionary biologists have long theorized that variation in DNA repair efficacy might explain some of the diversity of lifespan and cancer incidence across species, we have little data on the variability of normal germline mutagenesis outside of humans. Here, we shed light on the spectrum and etiology of mutagenesis across mammals by quantifying mutational sequence context biases using polymorphism data from thirteen species of mice, apes, bears, wolves, and cetaceans. After normalizing the mutation spectrum for reference genome accessibility and k-mer content, we use the Mantel test to deduce that mutation spectrum divergence is highly correlated with genetic divergence between species, whereas life history traits like reproductive age are weaker predictors of mutation spectrum divergence. Potential bioinformatic confounders are only weakly related to a small set of mutation spectrum features. We find that clock-like mutational signatures previously inferred from human cancers cannot explain the phylogenetic signal exhibited by the mammalian mutation spectrum, despite the ability of these signatures to fit each species’ 3-mer spectrum with high cosine similarity. In contrast, parental aging signatures inferred from human de novo mutation data appear to explain much of the 1-mer spectrum's phylogenetic signal in combination with a novel mutational signature. We posit that future models purporting to explain the etiology of mammalian mutagenesis need to capture the fact that more closely related species have more similar mutation spectra; a model that fits each marginal spectrum with high cosine similarity is not guaranteed to capture this hierarchy of mutation spectrum variation among species.
Branched-chain amino acid transaminase 1 regulates glioblastoma cell plasticity and contributes to immunosuppression
Authors: Pavle Boskovic, Nathalie Wilke, Ka-Hou Man, Peter Lichter, Liliana Francois, Bernhard Radlwimmer
Journal: Neuro-Oncology (2023)

Abstract Background Glioblastoma is the most common malignant brain tumor in adults. Cellular plasticity and the poorly differentiated features result in a fast relapse of the tumors following treatment. Moreover, the immunosuppressive microenvironment proved to be a major obstacle to immunotherapeutic approaches. Branched-chain amino acid transaminase 1 (BCAT1) was shown to drive the growth of glioblastoma and other cancers;however, its oncogenic mechanism remains poorly understood. Methods Using human tumor data, cell line models and orthotopic immuno-competent and -deficient mouse models, we investigated the phenotypic and mechanistic effects of BCAT1 on glioblastoma cell state and immunomodulation. Results Here, we show that BCAT1 is crucial for maintaining the poorly differentiated state of glioblastoma cells and that its low expression correlates with a more differentiated glioblastoma phenotype. Furthermore, orthotopic tumor injection into immunocompetent mice demonstrated that the brain microenvironment is sufficient to induce differentiation of Bcat1-KO tumors in vivo. We link the transition to a differentiated cell state to the increased activity of ten-eleven translocation demethylases and the hypomethylation and activation of neuronal differentiation genes. In addition, the knockout of Bcat1 attenuated immunosuppression, allowing for an extensive infiltration of CD8+ cytotoxic T-cells and complete abrogation of tumor growth. Further analysis in immunodeficient mice revealed that both tumor cell differentiation and immunomodulation following BCAT1-KO contribute to the long-term suppression of tumor growth. Conclusions Our study unveils BCAT1’s pivotal role in promoting glioblastoma growth by inhibiting tumor cell differentiation and sustaining an immunosuppressive milieu. These findings offer a novel therapeutic avenue for targeting glioblastoma through the inhibition of BCAT1.